This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Progress towards an HIV-1 vaccine has been stymied by the inability to induce a protective humoral response. Well-characterized neutralization epitopes are either poorly immunogenic or effectively masked on the majority of patient isolates. Newer evidence suggests that even highly masked primary isolates possess sensitive neutralization targets that are recognized by autologous patient sera and occasionally by heterologous sera. This suggests that mapping the epitopes involved may identify novel targets that are capable of inducing broadly neutralizing activities. In this project, we are identifying subtype B and C infected patients that possess broadly neutralizing activities for primary isolates, and localize the target epitopes. We are interested in antibody activities that mediate potent neutralization of heterologous viral envelope (Env) glycoproteins from various subtypes. We screened more than 100 plasma samples from subtype C HIV-1 for cross-neutralizing activities against heterologous Envs in order to discover novel targets that are exposed on typical neutralization-resistant primary isolates. In the past funding period, we identified a subtype C infected subject whose plasma possesses exceptional breadth and potency. We are in the process of characterizing the autologous viral Env and antibody neutralizing activity in this patient, as well as generating monoclonal antibodies from B cells.